Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan

• Published in: Japanese journal of clinical oncology Vol. 54; no. 8; pp. 930 - 938
• Main Authors: Takahashi, Naoto, Kondo, Takeshi, Ikari, Yuji, Fukumoto, Yoshihiro, Hatake, Kiyohiko, Masunari, Akira, Nishibayashi, Seiji, Kageyama, Akiko, Fukuta, Yasuhiko, Tojo, Arinobu
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 14-08-2024
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Arterial Occlusive Diseases - chemically induced; Arterial Occlusive Diseases - epidemiology; Epidemiology Note; Female; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - therapeutic use; Japan - epidemiology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Product Surveillance, Postmarketing; Pyridazines - administration & dosage; Pyridazines - adverse effects; Pyridazines - therapeutic use; Treatment Outcome; Young Adult; Japan; post-marketing surveillance; arterial occlusive events; chronic myeloid leukemia; ponatinib; acute lymphoblastic leukemia
• ISSN: 1465-3621; 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyae061

Abstract
Background
In September 2016, ponatinib was approved in Japan for the treatment of patients with chronic myeloid leukemia with resistance/intolerance to prior tyrosine kinase inhibitors and patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.
Methods
We conducted a post-marketing all-case surveillance to study the safety and efficacy of ponatinib in clinical practice, focusing on arterial occlusive events.
Results
Data from 724 patients were collected for 2 years from the initiation of ponatinib. The arterial occlusive events were reported in 6.49% (47/724) with an exposure-adjusted incidence rate of 6.8/100 person-years. The risks associated with arterial occlusive events were age and comorbidities including hypertension and diabetes. At 104 weeks, the cumulative major molecular response rate in patients with chronic-phase chronic myeloid leukemia was 67.2% and the complete cytogenetic response in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was 80.0%. Furthermore, the estimated 1-year overall survival rate was 98.5% for chronic-phase chronic myeloid leukemia and 68.6% for Philadelphia chromosome-positive acute lymphoblastic leukemia.
Conclusions
This surveillance demonstrated that ponatinib has a favorable safety and efficacy profile in Japanese patients and also showed the necessity of closely monitoring arterial occlusive events in older adults and patients with predisposing factors for atherosclerosis.
Ponatinib has a favorable safety and efficacy profile in Japanese patients: close monitoring of arterial occlusive events is indispensable among high-risk patients.